The establishment of an Oral Cancer Research Center is proposed by a group of 24 investigators from the University of Alabama at Birmingham. This well-funded group of investigators represent faculty from both basic and clinical science within the Schools of Medicine, of Dentistry, and of Public Health. Three major projects constitute the major focus of the Center on "Mechanisms of Initiation of Oral Tumors": PROJECT 1 will study the activation of the normally latent matrix metalloproteinase, collagenase, which cleaves collagen in the extracellular matrix. The hypothesis to be tested is that collagenase is activated in vivo by oral cancers, but not by normal tissue, to allow malignant oral tumor cells to cross the extracellular matrix and basement membrane. These studies may identify active collagenase as a biomarker for oral cancer. PROJECT 2 will study the role of human papillomaviruses in the development of oral cancers. Project 2 will test the hypothesis that the expression of human papillomavirus E6 and E7 oncogenes in oral neoplasms is important to the development of these tumors. PROJECT 3 will test the hypothesis that the homeostasis of basal cells in the oral epithelium is disrupted by local deficiencies in folate and vitamin B-12 and that these deficiencies are caused or exacerbated by alcohol and tobacco use. Project 3 deals with issues of molecular mechanism (local depletion of vitamins) and use of tobacco and alcohol as possible synergistic etiologic agents. Funds to establish a pilot project program are also requested. In the first two years, Dr. Michael Ruppert will use a novel assay system that he has developed to screen oral cancer cDNA libraries for new oncogenes. These new studies may provide new biomarkers for use as screening tools for oral cancers. Two shared core facilities will support the Center: The administrative core will handle the operation of the Center, the Biostatistics Core will expand our database in oral cancers and aid each project with data analysis. Other facilities available for use, but not financially supported by the Center, include Tissue Procurement, Oligonucleotide Synthesis, and Peptide Synthesis and Analysis. In addition, there are significant clinical, basic science, and administrative resources available to insure the success of the Center.